Dietary intake of an animal prostate preparation supplemented with zinc significantly improved diabetic conditions of rats and human subjects. The active ingredients in the prostate are zinc, arachidonic acid, cyclo(his-pro) and L-histidine. It is, thus, possible that a mixture of these chemicals can be a very useful gent for the treatment of diabetic patients. However, the amount of each chemical to be administered for the maximum results in controlling diabetes is not clearly established. The specific aims of this study are to determine the effects of zinc, cyclo(his-pro), arachidonic acid and L-histidine on the regulation of glucose metabolism in muscle tissues from normal and diabetic animals, and on the control of diabetic symptoms using genetically diabetic rat and mouse models. In this study, the optimal extracellular concentrations of each chemical for the glucose utilization will be determined. Then, the optimal levels of these chemicals are found in the human body, optimizing the oral intake of these endogenous compounds should not cause any adverse effect to human. Thus, this study may lead toward discovery of a very powerful commercial anti-hyperglycemic agent. PROPOSED COMMERCIAL APPLICATIONS: US patients were obtained for prostate extract supplemented with zinc in 1995 and 1998 for chemical composition for the treatment of diabetes. The first patented products (Pro-Z) are sold as a dietary supplement. The second patent product is not commercialized since no clinical data using these composition are available at present. Once, we developed this new drug, it will be one of the major anti-hyperglycemic agents for the treatment of diabetic patients in the world.